title: C9ORF72 transcription in a frontotemporal dementia case with two expanded alleles.
abstract: Discovery of intronic hexanucleotide repeat expansions of the C9ORF72 gene in a significant proportion of patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD)(1,2) was an important step for research into these disorders. The C9ORF72 genetic variant is more common than other described mutations and, unlike patients with mutations in SOD1, C9ORF72-ALS clinically and pathologically resembles the more numerous sporadic form.(3) However, progress has been limited by lack of understanding of the function of the C9ORF72 locus in health and disease. It is unknown whether the expansion causes disease by a gain of toxicity, or whether it disrupts expression of the wild-type protein encoded by the C9ORF72 gene, or some combination of both mechanisms.(1,2,4.)
authors.affiliation: From the Sheffield Institute for Translational Neuroscience (SITraN) (J.C.-K., A.H., N.B., J.J.B., J.K., P.J.S.), University of Sheffield; and the School of Biosciences (N.C.-R., N.N., V.L.B.), Cardiff University, UK.
authors.forename: Johnathan
authors.initials: J
authors.lastname: Cooper-Knock
authors.forename: Adrian
authors.initials: A
authors.lastname: Higginbottom
authors.forename: Natalie
authors.initials: N
authors.lastname: Connor-Robson
authors.forename: Nadhim
authors.initials: N
authors.lastname: Bayatti
authors.forename: Joanna J
authors.initials: JJ
authors.lastname: Bury
authors.forename: Janine
authors.initials: J
authors.lastname: Kirby
authors.forename: Natalia
authors.initials: N
authors.lastname: Ninkina
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Buchman
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Shaw
mesh_terms: D000073885:C9orf72 Protein; D004252:DNA Mutational Analysis; D042622:DNA Repeat Expansion / Q000235:genetics*; D005260:Female; D057180:Frontotemporal Dementia / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D011506:Proteins; D012333:RNA, Messenger